Normal domestic cats (Felis Catus), and cats with genetically determined GM2 gangliosidosis associated with inherited lysosomal beta-hexosaminidase deficiency, will be used in enzyme replacement therapy experiments, aimed at exploring possible strategies for enzyme therapy of human GM2 gangliosidosis. Biochemical and immunologic characterization of beta-hexosaminidase in normal and affected cats will be carried out to validate further the homology between feline disease and human GM2 gangliosidosis type II. Human placental and plasma beta-hexosaminidase forms will be infused in normal cats, to estabish procedure to be then applied to affected cats, with infusion of human or feline enzymes. Plasma clearance, organ disposition, subcellular location and endocellular survival of oxogenous enzyme will be studied by biochemical, electrophoretic and immunologic methods. Carbohydrate-specific recognition mechanisms determining preferential hepatic uptake of exogenous lysosomal enzymes will be studied for the formulation of organ-targeting procedures. The efficacy and safety of intermittent hyperbaric oxygen treatment, and alternate procedures, in inducing reversibly an increase in the permeability of the blood-brain barrier to exogenous beta-hexosaminidase will be evaluated. The possible therapeutic value of combined inhibition of liver uptake, induction of blood-brain barrier permeability, and beta-hexosaminidase injection will be assessed biochemically by effect on GM2 ganglioside storage in the brain of diseased cats; and clinically, by the possible effect in delaying the onset symptoms in enzyme deficient animals identified and treated in the first weeks of life.